Action potential, cardiac cells duration

Mechanism of action - Disopyramide is a class lA antiarrhythmic agent that decreases the rate of diastolic depolarization (phase 4), decreases the upstroke velocity (phase 0), increases the action potential duration of normal cardiac cells, and prolongs the refractory period (phases 2 and 3). It also decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and does not affect alpha- or beta-adrenergic receptors. 

Mechanism of Action A cardiac agent that prolongs duration of myocardial cell action potential and refractory period by acting directly on all cardiac tissue. Decreases AV and sinus node function. Therapeutic Effect Suppresses arrhythmias. Pharmacokinetics ... 

Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). Sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje cells display pacemaker activity (phase 4 depolarization). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. Thus, the PR interval is a measure of conduction time from atrium to ventricle, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential.

The effects of digitalis on the electrical properties of the heart are a mixture of direct and autonomic actions. Direct actions on the membranes of cardiac cells follow a well-defined progression an early, brief prolongation of the action potential, followed by shortening (especially the plateau phase). The decrease in action potential duration is probably the result of increased potassium conductance that is caused by increased intracellular calcium (see Chapter 14). All these effects can be observed at therapeutic concentrations in the absence of overt toxicity (Table 13-2). 

It has been suggested that bupivacaine may be more cardiotoxic than other long-acting local anesthetics (eg, ropivacaine). This reflects the fact that bupivacaine-induced blockade of sodium channels is potentiated by the long action potential duration of cardiac cells compared with nerve fibers. The most common electrocardiographic finding in patients with bupivacaine intoxication is a slow idioventricular rhythm with broad QRS complexes and eventually electromechanical dissociation. 

Furthermore, synchronization of contraction is facilitated by gap junctional communication as well as synchronization of electrical activation. The electrical coupling between cardiomyocytes mitigates differences in the membrane potential between these cells, for example in the course of an action potential if both cells repolarize at different timepoints. This results in smaller differences in the repolarization times thereby causing a reduction in the dispersion of the action potential duration. Since increased dispersion is known to make the heart more prone to reentrant arrhythmia, sufficient gap junctional communication can be considered as an endogenous arrhythmia-preventing mechanism. For a detailed discussion of the role of gap junctional communication in the biophysics of cardiac activation as related to anisotropy, nonuniformity and stochastic phenomena, see chapter 1 for a discussion of their role in arrhythmia, see chapter 6, and for a possible pharmacological intervention at the gap junctions for suppression of arrhythmia, refer to chapter 7. 

Standard microelectrode techniques were used to study the effects of isocorydine on potential characteristics of canine cardiac Purkinje fibers and ventricular myocardium in vitro. In the Purkinje fibers, the action potential durations APDjj and APD were prolonged at 3 pmol/1 but shortened at 30 pmol/1 by isocorydine. The action potential amplitude and maximal upstroke velocity were decreased at 100 pmol/1. In the ventricular myocardium, the action potential characteristics were changed by isocorydine at concentrations above 30 pmol/1. The APDJ0 was shortened, the APD90 was prolonged, and the maximal upstroke velocity was decreased at 30 pmol/1. The effective refractory period was prolonged by the alkaloid in Purkinje fibers and ventricular myocardium. These results indicated that the alkaloid may interfere with K+, Na+, and Ca+2 currents in myocardial cell membranes at different concentrations [287]. 

Table 2 The complete action potential duration (APD) and peak maximal voltage (PMV) change in various canine cardiac ventricular cells at a rate of 60 and 15 cycles per minute...

Except in certain minor details, the action potentials of vertebrate skeletal muscle resemble those of nerve cells. Action potentials of cardiac muscle or barnacle muscle, however, differ in certain respects from those of nerve and skeletal muscle. The most striking feature of the action potential in the ventricle of the heart is its long duration (see Figure 39), lasting up to 1 sec in amphibians. The upstroke of these action potentials is due primarily to inward current... 

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